論文 - 詳細
| RRC ID | 46532 |
|---|---|
| 著者 | Wu X, Shi Z, Cui M, Han M, Ruvkun G. |
| タイトル | Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes. |
| ジャーナル | PLoS Genet |
| Abstract |
The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene. |
| 巻・号 | 8(3) |
| ページ | e1002542 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pgen.1002542 |
| PII | PGENETICS-D-11-01180 |
| PMID | 22412383 |
| PMC | PMC3297578 |
| MeSH | Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Lineage* / genetics Cell Proliferation Chromatin* / genetics Chromatin* / metabolism Gene Expression Regulation, Developmental Germ Cells* / metabolism Mutation RNA Interference* Repressor Proteins* / genetics Repressor Proteins* / metabolism SUMO-1 Protein / genetics SUMO-1 Protein / metabolism |
| IF | 5.175 |
| 引用数 | 32 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2649 tm1637 tm894 tm1200 |